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Eflornithine and/or Sulindac in Preventing Recurrence of High-Risk Adenomas and Second Primary Disease in Patients with Stage 0-III Colon or Rectal Cancer

Status
Active
Cancer Type
Colon/Rectal Cancer
Unknown Primary
Trial Phase
Phase III
Eligibility
18 Years and older, Male and Female
Study Type
Prevention
NCT ID
NCT01349881
Protocol IDs
S0820 (primary)
U10CA037429
NCI-2012-02067
Study Sponsor
SWOG

Summary

This phase III trial studies how well eflornithine works compared to sulindac in preventing the return of the disease (recurrence) of high-risk adenomas and second primary disease in patients with stage 0-III colon or rectal cancer. Drugs used in chemotherapy, such as eflornithine and sulindac, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Objectives

PRIMARY OBJECTIVE:
I. To assess whether the combination of eflornithine and sulindac is effective in reducing the three-year event rate (high-risk adenomas and second primary colorectal cancers) in patients with previously treated stage 0-III colon or rectal cancer.

SECONDARY OBJECTIVES:
I. To assess whether the combination of eflornithine and sulindac (compared to corresponding placebos) has efficacy against colorectal lesions with respect to high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, any adenomas >= 0.3 cm, total advanced colorectal events, or total colorectal events.
II. To assess quantitative and qualitative toxicities of patients when treated with the combination of eflornithine and sulindac compared to corresponding placebos.
III. To evaluate a minimal set of tagging single nucleotide polymorphisms across multiple genes relevant to eflornithine and sulindac, in order to characterize associations with decreased adenoma/second primary colorectal cancer (CRC) risk and adverse events.
IV. To evaluate biomarker responses of treatment effect using novel microfluidics-based digital droplet detection system.
V. To explore the interaction of intervention arm and baseline statin use with respect to the 3-year event rate.
VI. To explore the interaction of the intervention arm and patient-reported meat consumption with respect to the 3-year event rate.
VII. To perform population pharmacokinetic (PK) analysis of eflornithine and sulindac in patients with previously treated stage 0-III colon or rectal cancer.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive eflornithine placebo orally (PO) once daily (QD) and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive eflornithine PO QD and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL PER PROTOCOL DATED 01/27/17)

ARM III: Patients receive eflornithine placebo PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL PER PROTOCOL DATED 01/27/17)

ARM IV: Patients receive eflornithine PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.

Eligibility

  1. STEP 0: REGISTRATION (Optional)
  2. Patients with a primary colon or rectal cancer resection who are potentially eligible for S0820 may be pre-registered at Step 0; patients registered to Step 0 will appear on an institutional patient tracking report; patients registered to Step 0 are not registered to the S0820 protocol; to participate in S0820, patients must be registered to Step 1 after patient is consented and evaluation of eligibility; patients registered to S0820 at Step 0 continuing to Step 1 registration must use the same Southwest Oncology Group (SWOG) patient identification (ID) for registration to S0820 Step 1
  3. STEP 1: REGISTRATION
  4. Patients must have a history of stage 0, I, II or III colon or rectal adenocarcinoma that has been treated per standard care with resection alone or in combination with radiation or chemotherapy; adjuvant chemotherapy and radiation therapy (RT) treatment must have been completed at least 30 days prior to registration
  5. Patients with history of segmental resections are eligible (i.e. right colectomy, extended right colectomy, transverse colectomy, left colectomy, extended left colectomy, sigmoid colectomy, low anterior resection, abdominoperineal resection); the definition of resection does not include endomucosal resection (EMR); patients that have received total proctocolectomy are ineligible * In addition to segmental resections, the following types of procedures are allowed: polypectomy: for Tis (stage 0) or pT1 patients only, resection may consist entirely of polypectomy (without completion of partial colectomy) if ALL of the following criteria are met: ** Single specimen, completely removed ** Negative margins of resection ** Grade 1 or 2 ** No angiolymphatic invasion * Transanal excision is allowed for pT1 rectal cancer patients with well or moderately differentiated tumors if National Comprehensive Cancer Network (NCCN) criteria for transanal excision are met, as stipulated here: ** NCCN Criteria for Transanal excision: *** < 3 cm in size *** T1 *** Grade 1 or 2 *** No lymphatic or venous invasion *** Negative margin *** Sm3 depth of tumor invasion is not allowed * When the lesion can be adequately identified in the rectum, transanal endoscopic microsurgery (TEM) may be used; TEM for more proximal lesions may be technically feasible
  6. Patients must be registered between 120 days and 456 days (inclusive) of primary resection; patients must show no evidence of colorectal cancer based on post-operative colonoscopy (performed at least 120 days after the colon or rectal resection date and prior to registration); patients with adenomas detected at the one-year postoperative colonoscopy are eligible if all adenomas have been completely removed
  7. Patients must have a pure tone audiometry evaluation to document air conduction within 30 days prior to registration; patients with hearing loss > 40 decibels (dB) in any of the five tested frequencies (250 Hertz [Hz], 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz) are not eligible; patients with active ear infections should be tested only after the acute phase of infection has resolved; for optimal results, it is recommended that testing be conducted by an audiologist, in a hearing test room, with insert earphones; Note: sites should not order audiometry evaluation until the potential participant has met all other eligibility criteria required for this study
  8. Patients must have a Zubrod performance status of 0-1
  9. Patients must have the ability to swallow oral medication
  10. Total white blood cells (WBC) >= 4.0 x 10^3/mcL (within 28 days prior to registration)
  11. Platelets >= 100,000/mcL (within 28 days prior to registration)
  12. Hemoglobin > 11.0 g/dL (within 28 days prior to registration)
  13. A total WBC >= 3.1 x 10^3/mcL is allowed for non-Hispanic black males (NHBM) and total WBC >= 3.4 x 10^3/mcL for non-Hispanic black females (NHBF) * Exception: If the WBC is lower than the above levels, the patient may be enrolled IF the absolute neutrophil count (ANC) is >= 1.3 for NHBM, >= 1.4 for NHBF, or >= 1.5 for all
  14. Serum bilirubin =< 2.0 mg/dL (within 28 days prior to registration)
  15. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x IULN (institutional upper limit of normal) (within 28 days prior to registration)
  16. Serum creatinine =< 1.5 x IULN obtained within 28 days prior to registration
  17. Patients with a prior malignancy or concurrent malignancy that is currently not being treated, whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, are eligible for this trial
  18. SPECIMEN SUBMISSION AND SUBSTUDY CRITERIA
  19. Patients must be offered the option to participate in submission of specimens for banking for future translational medicine studies
  20. Patients participating through PK sites, must be offered the option to submit blood specimens for population pharmacokinetic analysis
  21. Patients must be offered the option to participate in the Diet and Lifestyle Substudy
  22. REGULATORY CRITERIA
  23. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  24. As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Treatment Sites in Georgia

Emory Saint Joseph's Hospital


5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org

Emory University Hospital - Midtown


550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Northeast Georgia Medical Center - Gainesville


NGMC-Gainesville
Wisteria Building Suite 420
200 South Enota
Gainesville, GA 30501
770-219-8822
www.nghs.com

Study Coordinator:
Trena Davis BSN, RN, CRCC
770-219-8822

Doctors:

Andre M. Kallab MD
Richard J. LoCicero MD
Padma C. Nadella MD
Charles H. Nash, III MD, FACP
Geoffrey J. Weidner MD
Saloni H. Tanna MD
Christina A. Saurel MD

Piedmont Columbus Regional


1831 5th Ave
Columbus, GA 31901
www.columbusregional.com

Study Coordinator:
Jay Pitts, BS, CPhT
706-596-5426

Doctors:

Wilbur B. Bassett, Jr. MD
Andrew W. Pippas MD
Peter Q. Jiang MD
Suresh Nukala MD

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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